JACK KORYAN.
It was later that evening, and René was back home and at her computer with a glass of chardonnay and Silky in his basket at her feet. Over the hours she had let Nick’s words help her come to terms with the reality that she had done the right thing by her father. That at the time there were no other options. “
Promise me
this …”
She typed the name in the Google search box, and instantly a community newspaper site came up with several hits of the same article:
MAN COMATOSE FROM JELLYFISH ATTACK
A man was found washed up and unconscious on a beach on Homer’s Island. Jack Koryan of Carleton, Massachusetts, was barely alive after being stung by dozens of rare jellyfish while swimming.
Koryan was taken by emergency helicopter to the Cape Cod Medical Center … .
Scientists from Northeastern University and Woods Hole Institute said that Koryan had gotten caught in a large school of Solakandji jellyfish, which is only the size of a tennis ball but which has three-foot-long stinging tentacles. The highly venomous creature is a native of the waters of the Caribbean. Dr. Jason Marchi, a marine biologist from Woods Hole, said that the increased water temperature and the rise in nutrients from fertilizer runoff tend to support a rise in jellyfish populations … .
Like other species of toxic jellyfish, the Solakandji tentacles have millions of stinging cells called nematocysts … .
According to medical experts, there is currently no antivenom available for the Solakandji sting, which has caused deaths in Jamaica … .
She finished reading the story, then stretched out on the couch with her wine and Silky on her lap. She clicked on the television and lowered the volume just to decompress before getting ready for bed. On the news were the usual grim stories about the Iraq war and some local crime. She listened with
half interest. Something was bothering her and she could not put her finger on it. Something to do with that Jack Koryan guy—something that sat under the upper layers of her mind and kept sending up little tremors.
After maybe fifteen minutes of distraction, she got up and went back to the computer and did a search for
Solakandji,
the species of jellyfish Nick had. Amazingly, she got over three hundred hits. And she spent the better part of the next hour clicking on different sites. Most were divided between news stories of attacks, treatment of the stings, general information about jellyfish, and a few scientific papers. Several of the technical sites had photos of a creature that looked like a translucent mushroom with four interior rings and spaghetti tendrils.
The Solakandji jellyfish (related to Irukandji jellyfish of Australia’s Great Barrier Reef) is found in warm waters of the Caribbean and southern Atlantic.
Minor envenomations cause pain, swelling, and localized numbness that often subsides within hours of onset. Serious envenomations are associated with a rapid progression of symptoms, including erythema, paralysis, respiratory arrest, cardiac failure, and death … .
Other sites offered information about how to treat stings with vinegar, news stories about how victims in the Bahamas and elsewhere suffered a rapid rise in blood pressure and a cerebral hemorrhage that led to their deaths. Her mind returned to poor Jack Koryan in a deep sleep, unfortunate victim to happenstance, his entire universe reduced to a bed and that bank of monitors and destined never to open his eyes again.
She clicked onto more technical sites intended for dedicated marine scientists and scrolled down until she came to a dead stop.
N. A. Sarkisian, Mavros, N. T., et al. Neurotoxic activity on the sensory nerves from toxin of the deadly Solakandji tropical jellyfish
Chiropsalmus quadrigatus
Mason.
Chem Pharm Bull
17: 1086-8, 1971.
Mavros, N.T.
Nick. He had published a paper on the toxin thirty-five years ago. She read on.
The abstract described the Solakandji toxin as a novel proteolytic agent whose molecules functioned as an NMDA receptor antagonist. Furthermore,
the substance was identified as a glutamate inhibitor affecting aspartate—an excitatory amino acid-transmitter in the brain, similar to glutamate.
“Glutamate inhibitor affecting aspartate.”
The words jumped out at her.
That was the same neurochemical function that Jordan Carr had described—the same neurotransmitter was linked to seizure activity and agitated behaviors of people with dementia. By inhibiting glutamate, demented patients were demonstrating better behaviors and enhanced cognitive capabilities.
My God!
Jack Koryan was attacked by a jellyfish whose toxin was the chemical basis of Memorine. And Nick had helped pioneer the stuff.
“WHO THE HELL’S THIS COMMCARE WOMAN?”Gavin Moy’s eyes blazed down on Nick. He pulled a letter out of the folder. “René Ballard, Consulting Pharmacist. CommunityCare Pharmacy.” He handed the letter to Nick. “Isn’t she your friend?”
The letter was elegantly blunt, like a silver-plated bullet. “Yes, and former student,” Nick said.
“Well, your friend and former student says that medical records of some patients are missing—‘a violation of regulatory procedures,’ and she quotes the state and federal codes—blah, blah, blah—and she expects that all the records ‘complete and intact’ be returned immediately or she’s obligated to file a report with the IRB and request FDA review of our trial protocols. Jesus H. Christ!”
Nick had to repress the smile. “I believe she’s just doing her job.”
“Doing her job? She may be doing a job on friggin’ medical history.”
“Then maybe somebody should comply with her requests. Rumor has it that withholding nursing home records from consulting pharmacists is a violation of regulations.”
“Who the hell’s side you on?”
“Truth and beauty.” Nick smiled broadly.
Moy snickered. “Which is why I called you. But I must say, she has balls.”
“Because I taught her everything she knows.”
“Well, Jordan Carr says everything’s being returned, so tell her to wrap up.”
“What about the other nursing homes serving as research sites?”
“There, too. We want everything on the up-and-up.”
They were alone in Gavin Moy’s office at GEM Tech—a handsome, voluminous space with windows on two sides, one with a view of oak woodlands, the other commanding a view of the Boston skyline, shimmering in the distance.
On a table behind him were pictures of Moy’s wife, who had died five years ago. Moy had adjusted well to his widowerhood. Following her death he redirected his energy into his company, hiring the best and the brightest. And
now he was consulting senior medical execs and leaders in hospitals and academic institutions to put together a Dream Team of clinicians. Likewise, his board members were major venture capitalists who would have eaten their own children to be part of GEM’s future. And who wouldn’t—since Gavin Moy might be sitting on the pharmaceutical equivalent of the Holy Grail: a cure for Alzheimer’s disease in an ever-aging world.
On the wall behind his desk hung framed patents with his name on them—each for a variation of the same parent compound, just to keep competing labs from making look-alike compounds—the first, now faded, was dated January 10, 1976, the latest, from eight years ago, represented the final molecular structure whose trials would eventually be presented to the FDA for market approval. Trademarked Memorine, the compound not only had enormous pharmaceutical and commercial potential, if successful Gavin Moy could find himself in Stockholm, Sweden, when they passed out Nobel Prizes.
“We’re going to make an announcement at the meeting of shareholders in a few weeks, so the word will officially be out instead of leaks and speculations.”
It was a risky plan, because formal announcements about the success of a drug are almost never made in the middle of trials. But given the early success, Moy’s strategy was to create a market for Memorine before the first pill hit the shelves.
“Until then, we’re playing mum.”
Gavin Moy was paranoid and for good reason. He had sunk millions of his own and hundreds of millions of investors’ dollars into Memorine against a history of adventures that had turned out to be duds, including development of a cure for a rare neurological disorder; it proved disastrous in the Phase III clinical trials, costing GEM eighty million dollars and nearly tanking the company. Another agent targeting Parkinson’s disease was beaten to market when a competing lab offered a disgruntled GEM science director an offer he couldn’t refuse—the results: a look-alike that became a blockbuster while GEM fumbled around in Phase III trials only to scrap the project and end up with huge go-nowhere litigation fees. Those fiascoes were why Gavin Moy had guarded Memorine as if it were the Manhattan Project.
It was also why Nick had played coy with René. Only when she called to ask if the jellyfish connection was true did he confess a minor role in its development, breaking ethical protocol. Since learning about Memorine René had been flagellating herself with guilt for having consented to let her father die instead of holding out for some breakthrough cure. So he reiterated the
fact that the compound had not been targeted for clinical trials of dementia patients until two years after her father’s death. Even then Gavin Moy had sworn Nick and others to secrecy in face of the Darwinian competition for a cure and the fact that when the patent would run out in a few years generic knockoffs would fly. But before that eventuality, GEM hoped to establish a global franchise on Memorine.
“We’ve tried to keep a low profile, but we’re getting calls from physicians and AD organizations wanting to know if it’s true we’re working on a cure, can they volunteer patients. Christ, this is going to be the biggest thing since the Salk vaccine, maybe penicillin.”
“We can only hope.”
As Moy scanned Walden Woods out his window, Nick thought that he was like one of those reptiles with independent turretlike eyes constantly alert to opportunities and dangers. That was how he had been decades ago, and, perhaps, that was the secret of his successes and failures. On his desk was a brass plaque with the inscription: “It’s not over until you win.” Quintessential Gavin E. Moy.
Although Nick had seen Moy over the years at conferences and colloquia, they went back to a time before GEM Neurobiological Technologies existed. They were residents together at Mass General back in the late 1960s, when Gavin had started the forerunner of GEM Tech in the cramped basement behind MIT and where Nick helped in the research before finishing his residency. For years, some antecedent of Memorine had been in Moy’s pipeline, going through molecular reconfigurations and testing until the final form was developed. Today it was the flagship product for GEM Tech—and virtually their only product.
The promise began when it was discovered that the toxin from the Solakandji demonstrated an extraordinary neuronal property: it enhanced long-term memory. Fetal rodents injected with the compound learned to whip through complex mazes as if radar-directed while their untreated siblings stumbled along. Even more remarkable, mature rats demonstrated enhanced long-term recall, mastering maze problems that they hadn’t been exposed to since they were juveniles. The immediate thought, of course, was what it could do for people suffering memory loss—a speculation that raised hope against the scourge of Alzheimer’s disease.
The first breakthrough came when it was discovered that Memorine treatments had all but eliminated deposits of beta-amyloid peptides in mice genetically engineered to have an Alzheimer’s-like disease. Even more remarkable,
new brain cell growth explained why treated mice had higher learning curves and functionality than untreated mice. In short, Memorine had converted memory-degenerating rodents into recall wizards. Last year it was tested on human subjects and medical history began to be rewritten.
“Nick, you’ve read the reports—the results are fabulous and you could share in its success. So don’t tell me ‘no’ again, because I’m asking you to come aboard.” Moy’s eyes were shooting fire.
“Gavin, I’m very flattered, really.”
“On the contrary,
we’d
be flattered. And all bullshit aside, we’d like to have a man with your prestige and reputation.” Moy handed Nick a few sheets of paper. “Some of the people you’d be working with. I think you’ll recognize a few.”
It was a long and impressive list of physicians already taking part in the trials—names of medical researchers and practitioners associated with the best of institutions: the Scripps Institute, Yale, Washington University Medical School, the National Institutes of Health, et cetera.
“Plus some acquaintances of yours—Peter Habib, Jordan Carr, and others. We’re expecting the FDA to fast-track the application so we can get it to market in eighteen months.” Moy spoke with serene conviction. “Word is the president might support clinical development as a pledge to older voters in his reelection campaign. The long and short is this is a revolution, and we want you to be part of it.”
“And you’re working out possible ADRs—adverse drug reactions.”
Moy’s face froze. “What adverse drug reactions?”
“That woman who killed the CVS manager. I’ve also heard rumors of patients experiencing some deep-past delusional spells.”
“Where the hell did you hear that?”
It was actually Pete Habib who had come up with the “flashback” label. “Where I heard it isn’t important. The story of the murder was in all the newspapers. But questions have been raised about whether there’s a connection to the drug.”
The skin of Moy’s head flamed. “There is no connection, and there are no adverse drug reactions. These people were delusional psychotics suffering dementia. Christ, you see them all the time.”
“I’m just raising the possibility.”
Moy considered his words for a moment. His face suddenly lit up. “Then this is just the kind of thing we’d want you to monitor—making sure investigators look for contingencies, side effects, whatever. We need someone like
you with uncompromising integrity. But, believe me, there’s no connection between the woman who stabbed the store guy and Memorine, and you can take that to the bank.”
“Okay, but why do you want me when you have all these top people?”
“Because I’d like you to direct the phase three clinical study, to be chief principal investigator—to coordinate all trial data for our FDA application. I want you at the top.”
Nick did not see that coming. “Why not Pete Habib? He’s chief neurologist at South Shore and one of the best around. Or Jordan Carr?”
“I said no bullshit: You’re senior neurologist at MGH and chief administrator of the imaging lab, and Peter Habib, Jordan Carr, and the rest aren’t. Having you in the lead would draw a lot of attention, not to mention investors.”
“That’s quite an honor, but to do this right will require a large commitment.”
“Of course, and you’ll be compensated handsomely.”
“I’m talking time, not money. I’ll have to think about it and talk it over with Thalia.”
“Of course.” Moy glanced at his watch. “How’s tomorrow by noon?” Nothing in Moy’s face said he was being humorous.
“Next week.”
“All right, next week.” Moy leaned into a huddle. “Okay, the ugly stuff: For your own patients, we’re offering you twice the standard trial rate—three thousand dollars per patient visit. We expect twelve to fifteen visits. You have a lot of AD patients and you can do the math. In addition, for all your expertise blah blah blah and the privilege of having you as clinical director blah blah blah … we’re offering you equity in the company in the form of stocks—the numbers to be worked out.
“As you know, about five million people suffer Alzheimer’s in the States alone—a figure that’s going to double by 2020. The current market is twelve billion dollars for AD meds. We’ve created a special unit to market Memorine, lined up the third largest pharmaceutical company in the country to distribute, plus a sales force of seven hundred reps on a sales-based bonus system to promote it to practitioners. We’ve got a projection of three million prescriptions the first year on the shelves, twice that the next year, and multiples once our foreign subsidiaries kick in. Nick, this is a fifty-billion-dollar pill. And for the clinical director and the researchers associated with it, the benefits are incalculable.”
Nick smiled. “At least you’re not turning up the pressure.”
“Hell, I’m just winding up. Your imaging lab is a critical tool toward our end, and our board has authorized a ten-million-dollar grant for its application in the trials, which should cover overhead and salaries, blah blah blah. What do you say?”
Nick was aware of the prestige of being part of the development of a potential miracle drug. But at his age he was not out for glory or the financial rewards—and he
could
do the math. Being a millionaire several times over did not move Nick. He and Thalia did not have extravagant tastes. They lived comfortably in Wellesley and drove a seven-year-old Saab. They vacationed in Fresno because Thalia had family there and Nick liked to hike the Sierras with his cameras. Because of ill health, Thalia no longer worked, nor did they miss her income now that their children were on their own. Money was never a motivating force in Nick’s life. And, like René, he harbored old-fashioned academic cynicism toward clinicians participating in studies with drug companies.
But the majority of physicians conducted trials for higher ethical reasons: to benefit humankind. And Nick was one of them. As embarrassing as the financial benefits would be, Nick was hearing that he could be part of a team that might cure Alzheimer’s disease—a nemesis that he personally had confronted for most of his professional life—a disease more vicious than cancer since it robbed a victim first of selfhood, then of life.
“You should know that I’ve been cutting back on my practice and research.”
“Christ, you’re only sixty-two-too early to be retiring. Think of the hundreds, maybe thousands of people and patients you’ve watched waste away with dementia. Two or three years from now, when the world is singing ‘hallelujah’ because the scourge of the aging world has been defeated, where you going to be, huh?—on top of some mountain taking snaps of yellow-belly sapsuckers.”